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Anthrax, whether resulting from natural or bioterrorist-associated exposure, is a constant threat to human health. Bacillus anthracis is the causative agent of anthrax. It is surrounded by a polypeptide capsule of poly-gamma-D-glutamic acid (gamma-D-PGA), which is essential for virulence, is poorly immunogenic and has anti-phagocytic properties. Antibodies to the capsule have been shown to enhance phagocytosis and killing of encapsulated bacilli.

Niemann-Pick Disease, type C (NPC) is a rare, autosomal recessive, neurodegenerative disease. Approximately 95% of patients with NPC have mutations in NPC1, a gene implicated in intracellular cholesterol trafficking. Mutation of NPC1 causes intracellular accumulation of unesterified cholesterol in late endosomal/lysosomal structures and marked accumulation of glycosphingolipids, especially in neuronal tissue. Thus, NPC patients generally present with hepatosplenomegaly (enlargement of liver and spleen) and neurological degeneration.

The technology describes the composition of small molecule compounds that are antagonists of the P2Y14 receptor. Also provided are methods of using the compounds, including a method of treating a disorder, such as inflammation, diabetes, insulin resistance, hyperglycemia, a lipid disorder, obesity, a condition associated with metabolic syndrome, and asthma, and a method of antagonizing P2Y14 receptor activity in a cell.

The technology discloses composition of compounds that fully antagonize the human P2Y14 receptor, with moderate affinity with insignificant antagonism of other P2Y receptors. Therefore, they are highly selective P2Y14 receptor antagonists. Even though there is no P2Y14 receptor modulators in clinical use currently, selective P2Y14 receptor antagonists are sought as potential therapeutic treatments for asthma, cystic fibrosis, inflammation and possibly diabetes and neurodegeneration.

The coronavirus disease 2019 (COVID-19) is caused by a novel RNA enveloped coronavirus, SARS-CoV-2 when the virus enters human airway cells via an ACE2-mediated entry process. This entry pathway is facilitated by the cell surface heparan sulfate proteoglycan (HSPG), which enhances viral attachment to the cell surface. Researchers at NIDDK and NCATS have discovered a collection of FDA-approved drugs that can interfere with the entry of SARS-CoV-2. These drugs can be grouped into three classes based on the distinct steps in the viral entry pathway that they target.

Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis and is associated with nearly 200,000 cancers and 140,000 deaths each year. EBV-associated cancers include Hodgkin's lymphoma, non-Hodgkin's lymphoma, Burkitt B cell lymphoma, and EBV post-transplant lymphoproliferative disease. The latent reservoir for EBV in the body is the B lymphocyte. Thus, blocking B cell infection is important for reducing EBV-related disease.

During lung infection, bloodstream neutrophils (PMNs) responding to infection travel to the airspace lumen. Although successful arrival of microbicidal PMNs to the airspace is essential for host defense against inhaled pathogens, excessive accumulation of PMNs in the lung contributes to the pathogenesis of several prevalent lung disorders, including acute lung injury, bronchiectasis, and COPD. Unfortunately, there is no treatment for controlling PMN accumulation in the lung.

Immunoglobulins play a key role in the immune system. CDC has developed and tested hybridoma cell lines (monoclonal antibody (mAb) clones) for human IgG and other immunoglobulins. The mAbs generated from those hybridomas could be used as a reagent (second Ab) of anti-human immunoglobins in a diagnostic assay for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus that causes COVID-19 (coronavirus disease 2019) and other assays that detect antigen specific antibodies from human sera.

This technology includes the development and use of small molecule activators of pyruvate kinase (PK) for the treatment of inherited nonspherocytic hemolytic anemia, including PK deficiency. PK deficiency is caused by an inherited deficiency in an enzyme that reduces the lifespan of red blood cells. More than 150 unique mutations have been identified in the PK gene that lead to decreased activity in this essential enzyme in the glycolytic pathway. The prematurely lysed red blood cells can lead to jaundice, splenomegaly, and a hemolytic anemia.

This technology includes the identification and use of niclosamide analogs and prodrugs for the treatment of SARS-CoV-2 infection. In-vitro studies have found niclosamide, an old anthelminthic drug, to be potent and effective against Covid-19. But the broad antiviral effect of niclosamide is offset by the low solubility of the drug, leading to poor oral absorption. The niclosamide analogs and prodrugs included in this technology have better in vitro physicochemical properties. Also, these analogs were comparable to niclosamide in the in-vitro 3D models of SARS-CoV-2 infection.